Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

新时代检验医学发展定位与思考

检验医学作为医学科学的重要支撑学科,在疾病早期诊断、病情监测、预后判断与风险评估等方面发挥着重要作用。21世纪是数字信息时代,高新检测技术、计算机科学及互联网大数据等,为检验医学的发展带来巨大的机遇与挑战,新时代下如何借助信息科技革命实现检验医学新发展是检验工作者面临的重要课题。该文回顾检验医学的发展历程,重点关注检验医学在新时代的发展定位及未来发展方向,以求开创检验医学发展新局面。     

Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent

Benzophenone-3 is a putative endocrine disrupting chemical and common ingredient in sunscreens. The potential of endocrine disrupting chemicals to act as agonists or antagonists in critical hormonally regulated processes, such as mammary gland development and mammary tumorigenesis, demands evaluation of its potential in promoting breast cancer. This study identifies the effects of BP-3 on mammary tumorigenesis with high-fat diet during puberty versus adulthood in Trp53-null transplant BALB/c mice. Benzophenone-3 exposure yielded levels in urine similar to humans subjected to heavy topical sunscreen exposure. Benzophenone-3 was protective for epithelial tumorigenesis in mice fed lifelong low-fat diet, while promotional for epithelial tumorigenesis in mice fed adult high-fat diet. Benzophenone-3 increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity dependent on specific dietary regimen and tumor histopathology. Even in instances of an ostensibly protective effect, other parameters suggest greater risk. Although benzophenone-3 seemed protective on low-fat diet, spindle cell tumors arising in these mice showed increased proliferation and decreased apoptosis. This points to a need for further studies of benzophenone-3 in both animal models and humans as a potential breast cancer risk factor, as well as a more general need to evaluate endocrine disrupting chemicals in varying dietary contexts.     

Avian mud nest architecture by self-secreted saliva

Mud nests built by swallows (Hirundinidae) and phoebes (Sayornis) are stable granular piles attached to cliffs, walls, or ceilings. Although these birds have been observed to mix saliva with incohesive mud granules, how such biopolymer solutions provide the nest with sufficient strength to support the weight of the residents as well as its own remains elusive. Here, we elucidate the mechanism of strong granular cohesion by the viscoelastic paste of bird saliva through a combination of theoretical analysis and experimental measurements in both natural and artificial nests. Our mathematical model considering the mechanics of mud nest construction allows us to explain the biological observation that all mud-nesting bird species should be lightweight.

Bird nests come in a variety of forms made from diverse building materials (1, 2). Each type of bird nest is subjected to mechanical constraints imposed by material characteristics. To overcome these constraints, birds have devised brilliant architectural technologies, which provide inspiration for a novel materials processing scheme and help us to better understand animal behavior.For instance, some birds including storks (Cicioniidae) and eagles (Accipitidae) build nests by piling up hard filamentary materials such as twigs, harnessing their friction as the cohesion mechanism (3). Weaverbirds (Ploceidae) weave soft filamentary materials such as grass and fine leaves into a woven nest tied to a tree branch. Some bird species use their own saliva in nest building, which Darwin considered an example of natural selection (4). An extreme case is the Edible-nest Swiftlets, which build their nest purely of self-secreted saliva so that it can be attached to cliff walls and cave ceilings where the above twig piles and tied leaves are not allowed (5).Swallows (Hirundinidae), phoebes (Sayornis), and other mud nesters have developed a unique building material, a mixture of mud and their own saliva, in contrast to those made of purely collected or self-secreted materials (6) (Fig. 1). During construction, mud nesters repeatedly pile a beakful of wet mud on the nest, and liquid bridges are formed in the nest due to evaporation. While building a nest usually takes several weeks, a transition from wet to dry structures can occur within a few hours. Hence, the capillary forces of liquid bridges temporarily provide cohesion such as those in sandcastles. However, unlike sandcastles, dehydrated saliva comes into play for permanent cohesion after complete evaporation (SI Appendix, Supplementary Note 1).Open in a separate windowFig. 1.A nest of the barn swallow (H. rustica). (A) Photograph of a barn swallow nest, taken from under the ceiling of a house in Suwon-si, Gyunggi-do, South Korea (37°16′13.5″N 126°59′01.0″E). (B) SEM image of the nest surface. (C) Chemical composition analysis of the surface shown in B by EDS. The red area indicates a region containing mostly carbon atoms, which may originate from bird saliva. The green area indicates a region containing mostly the silicon atoms of clay particles.Mud itself cannot confer sufficient cohesion and adhesion in mud nests. The ability of mud nests to bear tensile loads originates from the gluing agent in the bird''s saliva, which permeates into granules as a liquid and binds them as a solid after solvent evaporation (6–8) (SI Appendix, Supplementary Note 2). The gluing agent is called mucin, a family of large glycoproteins that are ubiquitous in animal organs and form a mucus gel with versatile functionality (9). Fig. 1B shows the scanning electron microscopy (SEM) image of a barn swallow’s mud nest consisting of platelet clay particles and larger grains. Energy-dispersive spectroscopy (EDS) mapping image of Fig. 1C clearly shows regions corresponding to organic material which is presumed to be from bird’s saliva.Of particular interest and worth biophysical investigation are the tensile strength of the mud nest with hardened saliva, design principles associated with the saliva-originated strength, and the resulting effects on the evolution of these mud-nesting birds. Principles behind cohesion in granular materials, such as wet sands (10), cemented powder aggregates (11), construction materials (12), and pharmaceutical tablets (13), have been studied to date, exploring the stress transmission, elasticity, and failure (14–18), and the formation of solidified bridges (19–21). However, little attention has been paid to the cohesion effects of self-secreted polymer materials upon evaporation and the biologically constructed granular architecture like birds’ mud nests. Here we devised experimental techniques to measure the strength of the relatively small and fragile nest specimens in order to mechanically characterize birds’ mud nests. We elucidate how solutes from bird saliva generate solid bridges that give rise to macroscopic tensile strength, which has long awaited physicochemical explanation since its first observation (4). To characterize the design principle of bird''s mud nests, we investigated natural and three-dimensional (3D)-printed artificial nests with various tools for visualization and mechanical testing. Along with the experimental studies, we theoretically investigated the effects of biopolymer concentration on nest strength. This combination of theory and experiment suggests that there is a size limit for mud-nesting birds, which is supported by biological data.     

A novel H7N3 reassortant originating from the zoonotic H7N9 highly pathogenic avian influenza viruses that has adapted to ducks

The first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in March 2013 in China. This virus continues to circulate in poultry in China while mutating to highly pathogenic AIVs (HPAIVs). Through monitoring at airports in Japan, a novel H7N3 reassortant of the zoonotic H7N9 HPAIVs, A/duck/Japan/AQ‐HE30‐1/2018 (HE30‐1), was detected in a poultry meat product illegally brought by a passenger from China into Japan. We analysed the genetic, pathogenic and antigenic characteristics of HE30‐1 by comparing it with previous zoonotic H7N9 AIVs and their reassortants. Phylogenetic analysis of the entire HE30‐1 genomic sequence revealed that it comprised at least three different sources; the HA (H7), PB1, PA, NP, M and NS segments of HE30‐1 were directly derived from H7N9 AIVs, whereas the NA (N3) and PB2 segments of HE30‐1 were unrelated to zoonotic H7N9. Experimental infection revealed that HE30‐1 was lethal in chickens but not in domestic or mallard ducks. HE30‐1 was shed from and replicated in domestic and mallard ducks and chickens, whereas previous zoonotic H7N9 AIVs have not adapted well to ducks. This finding suggests the possibility that HE30‐1 may disseminate to remote area by wild bird migration once it establishes in wild bird population. A haemagglutination‐inhibition assay indicated that antigenic drift has occurred among the reassortants of zoonotic H7N9 AIVs; HE30‐1 showed similar antigenicity to some of those H7N9 AIVs, suggesting it might be prevented by the H5/H7 inactivated vaccine that was introduced in China in 2017. Our study reports the emergence of a new reassortant of zoonotic H7N9 AIVs with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.